Novel Agents in Chronic Lymphocytic Leukemia: New Combination Therapies and Strategies to Overcome Resistance.
Novel Agents in Chronic Lymphocytic Leukemia: New Combination Therapies and Strategies to Overcome Resistance.
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DOI：
10.3390/cancers13061336
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发表时间：
2021-03-16
期刊：
影响因子：
5.2
通讯作者：
Eichhorst B
中科院分区：
文献类型：
--
作者：
Fürstenau M;Eichhorst B
如今，许多慢性淋巴细胞白血病（CLL）患者接受所谓的新药治疗，包括BTK抑制剂、Bcl-2抑制剂和PI3K抑制剂。由于 CLL 是一种慢性疾病，大多数患者在使用这些药物治疗时或治疗后会复发，并且已经描述了这种对新药耐药性背后的各种机制。在这篇综述中，我们提出了关于新药耐药性的当前证据，讨论了预防其发展的方法，并为已经产生耐药性的患者的治疗提供了指导。 Bruton 的酪氨酸激酶 (BTK) 抑制剂（如 ibrutinib 和 acalabrutinib）以及 Bcl-2 抑制剂 Venetoclax 的批准彻底改变了慢性淋巴细胞白血病 (CLL) 的治疗。虽然这些新药单独或联合使用可在大多数 CLL 患者中引起持久和深度缓解，但它们的使用可能与临床耐药性的发展有关。在这篇综述中，我们阐明了对 BTK 和 Bcl-2 抑制的获得性抗性的遗传基础，并提供了与影响这些靶蛋白的单一基因组改变无关的抗性机制的证据。本综述讨论了防止新药耐药的策略，特别关注新的联合疗法。
Nowadays, many patients with chronic lymphocytic leukemia (CLL) are treated with so-called novel agents, including BTK inhibitors, Bcl-2 inhibitors and PI3K inhibitors. As CLL is a chronic disease, most patients will relapse on or after treatment with these drugs and various mechanisms behind this resistance to novel agents have been described. In this review, we present the current evidence on resistance to novel agents, discuss approaches to prevent its development and provide guidance on the treatment of patients who have already acquired resistance. The approval of Bruton’s tyrosine kinase (BTK) inhibitors such as ibrutinib and acalabrutinib and the Bcl-2 inhibitor venetoclax have revolutionized the treatment of chronic lymphocytic leukemia (CLL). While these novel agents alone or in combination induce long lasting and deep remissions in most patients with CLL, their use may be associated with the development of clinical resistance. In this review, we elucidate the genetic basis of acquired resistance to BTK and Bcl-2 inhibition and present evidence on resistance mechanisms that are not linked to single genomic alterations affecting these target proteins. Strategies to prevent resistance to novel agents are discussed in this review with a special focus on new combination therapies.
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影响因子：
20.3
作者：
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通讯作者：
Roberts, Andrew W.
影响因子：
51.1
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影响因子：
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Kipps, Thomas J.
慢性淋巴细胞白血病患者对 BTK 抑制产生耐药性的克隆进化
影响因子：
16.6
作者：
Burger JA;Landau DA;Taylor-Weiner A;Bozic I;Zhang H;Sarosiek K;Wang L;Stewart C;Fan J;Hoellenriegel J;Sivina M;Dubuc AM;Fraser C;Han Y;Li S;Livak KJ;Zou L;Wan Y;Konoplev S;Sougnez C;Brown JR;Abruzzo LV;Carter SL;Keating MJ;Davids MS;Wierda WG;Cibulskis K;Zenz T;Werner L;Dal Cin P;Kharchencko P;Neuberg D;Kantarjian H;Lander E;Gabriel S;O'Brien S;Letai A;Weitz DA;Nowak MA;Getz G;Wu CJ
通讯作者：
Wu CJ